对不同的丝状状态的结构洞察力揭示了细菌STING激活的调节机制
Yuchao Yang1, Yueyue Liu1, Xue Ma2
1Shanxi Key Laboratory for Modernization of Traditional Chinese Veterinary Medicine (TCVM), College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
mBio
|August 14, 2025
概括
细菌使用基于循环寡核酸的抗菌体信号系统 (CBASS) 来对抗菌体. 这项研究表明,细菌STING蛋白如何改变结构,由调节,以激活防御并保护细菌群体.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 循环寡核酸基抗菌体信号系统 (CBASS) 是一种与真核生物cGAS-STING通路相关的细菌免疫机制.
- CBASS使用循环二核酸来通过堕胎细胞死亡触发对菌体感染的防御.
- 细菌STING蛋白在结合联体后聚合成丝,但不同的丝状况和它们的功能尚不清楚.
研究的目的:
- 为了解决与3'3'-c-di-GMP结合的 *Epilithonimonas lactis* TIR-STING (*El*STING) 的冷EM结构.
- 阐明不同状元在调节纳酶活性中的功能作用.
- 了解离子在激活和线形成中的调节作用.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定的结构.
- 生物化学测试以评估NADase活性.
- 不同的寡合体状态 (螺旋纤维和纤维束) 的结构分析.
主要成果:
- 解决了两个*E*STING寡合状态:不活跃的螺旋丝和活跃的纤维束.
- 螺旋丝扣留BB循环,抑制NADase活动,由CBDα4螺旋和稳定.
- 纤维束的形成破坏了自身抑制的接触,使NADase活动,与双调节组合.
- 该机制与其他细菌的STING系统有所不同,突出显示了进化多样性.
结论:
- 截然不同的导线架构作为细菌STING激活的结构检查点.
- 符合可塑性和离子通过ElSTING调节流产性感染.
- 这些发现揭示了 prokaryotic 和 eukaryotic 病原体防御中的保存原则,在抗菌疗法中具有潜在的应用.
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